Behavioral relevance of hippocampal pattern separation and completion processes

两个被认为对记忆功能至关重要的关键过程是模式分离，或为类似事件和模式完成创建不同记忆的能力，或在呈现稍微不同的信息版本时检索先前学习过的信息的过程。先前的大量研究强调，海马体非常适合执行这两项与存储和检索不同记忆有关的关键功能。然而，目前尚不清楚模式分离和模式完成过程如何与行为相关。为了充分了解海马功能的基本机制以及与海马功能障碍相关的精神健康疾病，了解这些海马核心过程如何与人类记忆相关是至关重要的。本研究使用高分辨率功能性磁共振成像（fMRI）来研究人类海马体区域的反应如何与模式分离和完成过程以及行为记忆的测量相关。在目标1中，我们将询问海马体中的模式分离和完成是否与内隐行为记忆判断有关。除了这个基础研究问题，我们还将在Aim 1中进行转化研究，将我们的结果与目前在平行行为范式中收集的单个神经元记录进行比较。这将允许比较人类和动物模型之间的海马网络功能，以直接评估动物模型对理解人类记忆形成的贡献。目的2将解决模式分离和完成过程是否在整个人类海马的分布活动模式水平上表现出来的问题。分布式海马活动模式和明确的行为分类之间的关系将被评估，以询问这些活动模式是否对行为决策很重要。总之，该建议将通过在内隐和外显行为记忆任务中执行高分辨率fMRI来解决人类海马功能如何与行为相关的重要问题。这项工作对于理解人类海马功能的基本机制以及这些机制在疾病状态下是如何出错的至关重要。

Two key processes thought to be critical for memory function are pattern separation, or the ability to create distinct memories for similar events and pattern completion, or the process of retrieving previously learned information when presented with a slightly different version of the information. A large body of previous work stresses that the hippocampus is ideally suited to perform both of these crucial functions pertaining to storing and retrieving distinct memories. However, it is currently unknown how pattern separation and pattern completion processes are related to behavior. It is critical to understand how these core hippocampal processes are indeed relevant for human memory in order to fully understand the basic mechanisms of hippocampal function as well as mental health diseases associated with hippocampal dysfunction. This proposal uses high-resolution functional magnetic resonance imaging (fMRI) to investigate how responses in regions of the human hippocampus are related to pattern separation and completion processes and measures of behavioral memory. In Aim 1, we will ask if pattern separation and completion in the hippocampus are associated with implicit, behavioral memory judgments. In addition to this basic research question, we will engage in translational research in Aim 1 by comparing our results to single neuron recordings currently being collected in a parallel behavioral paradigm. This will allow for the comparison of hippocampal network function between humans and animal models to directly evaluate the contributions of animal models for understanding memory formation in humans. Aim 2 will address the question of whether pattern separation and completion processes are manifested at the level of distributed patterns of activity across the entire human hippocampus. The relationship between distributed hippocampal activity patterns and explicit behavioral categorizations will be assessed to ask if these activity patterns are important for behavioral decisions. In sum, this proposal will address important questions of how human hippocampal function is related to behavior by performing high-resolution fMRI during implicit and explicit behavioral memory tasks. This work is essential for understanding basic mechanisms of human hippocampal function and how these mechanisms go awry in disease states.